[Truncated abstract] First metatarsophalangeal joint (MTPJ1) motion is an important factor in normal weight transference during walking. Disruptions to normal range can influence joints both proximal and distal to the MTPJ1, potentially leading to pain and dysfunction. Whilst the MTPJ1 has been investigated significantly, the numerous methodologies described to quantify range of motion can be questioned and makes comparisons difficult. Range of MTPJ1 motion is commonly assessed in a clinical setting to determine pathology as well as to make decisions on appropriate intervention. The anatomical and biomechanical influence of tendo Achilles load and MTPJ1 motion has been well described; however few studies measuring MTPJ1 range control for Achilles load or describe ankle joint positioning. Further to this the effects of reducing tendo Achilles stiffness on MTPJ1 extensions has yet to be investigated. The purpose of this study was to describe a technique to quantify passive MTPJ1 extension and to determine the influence of ankle joint position on joint range. Secondly the effect of calf muscle stretching on MTPJ1 range was also investigated. The information gathered will assist both research and clinical protocols for quantifying MTPJ1 range, and provide a greater understanding of the anatomic and biomechanical relationship between tendo Achilles load and MTPJ1 extension. In order to fulfil the purposes of the study it was necessary to establish a reliable methodology to quantify non weight bearing MTPJ1 extension. Reliability testing was undertaken in three parts. '...' The results demonstrated a statistically significant increase in joint range immediately following a one minute stretch for variables ankle joint range of motion as well as MTPJ1 extension for ankle joint plantar flexed at 10 Newton's and ankle joint neutral and plantar flexed at 30 Newtons. No significant differences were noted in ankle or MTPJ1 range of motion in either the control group on immediate re-testing, or in both groups after a one week stretch program. The findings of this study support those documented in the literature pertaining to the ankle joint position, tendo Achilles load and plantar fascial stiffness to MTPJ1 range of motion. Increased stiffness at the MTPJ1 was noted dependant on ankle joint position from ankle joint plantar flexion through to ankle joint dorsiflexion. This appears most likely due to increases in tendo Achilles load and subsequent forces transmitted to the plantar aponeurosis. The present study also demonstrated a trend towards increased joint extensibility and limb dominance. The study also supports previous literature into gender differences and joint extensibility, with a positive trend towards increased MTPJ1 range evident in the female subjects tested. The study also demonstrated the immediate effect of calf muscle stretching on ankle and MTPJ1 range of motion. It remains however unclear as to the exact mechanisms involved in producing increased joint range be it reflex inhibition or actual changes to the viscoelastic properties of the soft tissues. Despite this, no changes were evident following a one week stretching program, which supports previous literature describing a short lag time before soft tissues revert to baseline length properties following a single stretch session.

Stretching is a widely prescribed technique that has been demonstrated to increase range of motion. Consequently it may enhance performance and aid in the prevention and treatment of injury. Few studies have investigated the frequency of stretching on a daily basis. The purpose of this study was to investigate the effect of stretching frequency on range of motion at the ankle joint. The detraining effect was also investigated after a period without stretching. Thirty-one female subjects participated in this study. They were randomly assigned to a control group who did not stretch a group who stretched two times per week (Stretch-2) or a group who stretched four times per week (Stretch-4). The stretching intervention was undertaken over four weeks and targeted the gastrocnemius and soleus muscles. Each stretch was held for duration of 30 seconds and repeated five times. Prior to the intervention (PRE), dorsiflexion was measured using a weights and pulley system that passively moved the ankle joint from a neutral position into dorsiflexion. After the four week stretching period (POST), dorsiflexion was measured once again to determine the change following the stretching programme. Following a further four week period where no stretching took place (FINAL), dorsiflexion was measured to determine the detraining effect. Electromyography was used to monitor the activity of the plantarflexors and dorsiflexors during the measuring procedure. The results of the study showed a significant increase in ankle joint range of motion for the Stretch-4 group (p<0.05) when comparing PRE and POST measurements. The Stretch-2 and control groups did not show significant differences (p>0.05) between PRE and POST measurements. When comparing the PRE and FINAL measurements of the Stretch-4 group, no significant differences were recorded (p>0.05). The POST and FINAL measurements were significantly different (p<0.05). After the detraining period the Stretch-4 group lost 99.8% of their range of motion gains. The present data provide some evidence that the viscoelastic properties of the muscle stretched were unchanged by the four week static stretching programme. The mechanism involved in the observed increase in range of motion for the Stretch-4 group is possibly that of enhanced stretch tolerance of the subject. Further research is required to support this conjecture.

Stretch of cardiac muscle is known to activate various physiological processes that result in changes to cardiac function, contractility and electrophysiology. To date, however, the precise relationship between mechanical stretch and changes in the electrophysiology of the heart remain unclear. This relationship, termed mechanoelectric feedback (MEF), is thought to underlie many cardiac arrhythmias associated with pathological conditions. These electrophysiological changes are observed not only in the whole heart, but also at the single cardiomyocyte level, and can be explained by the presence of stretch-activated ion channels (SACs). Most investigations of the actions of stretch have concentrated on these sacrolemmal ionic currents thought responsible for the proposed MEF-induced changes in contractility. While these studies have provided some useful insight into possible mechanisms, the inappropriate use of solutions and non-physiological degrees of stretch, may have caused somewhat misleading results. Currently, little is known about the involvement or contribution of non-selective or K+ selective SACs to the normal cardiac cycle. Here, I investigate the concept that stretch-induced changes in cardiac electrophysiology (MEF) are important in normal cardiac cycle and demonstrate the effects of stretch on the Frank-Starling mechanism (stretch induced increases in cardiac contractility) while pharmacologically manipulating stretch-activated ion currents. Experiments were conducted using a number of agents known to influence stretch-activated channels either in a positive or antagonistic manner. Results proved somewhat negative toward MEF theory with only substantial or pathological levels of stretch being able to elicit any electrophysiological change in the heart. Furthermore, where electrophysiological changes were associated with pathological stretch they were not consistently modulated by stretch-activated ion channel activators or blockers. Of equal importance was the observation that smaller levels of myocardial stretch associated with positive changes in contractility via the Frank-Starling mechanism were not associated with any electrophysiological changes in the Langendorff perfused heart (as observed by monophasic action potentials) nor in isolated muscle preparations (as observed through transcellular membrane potential recordings). As such, the present research undertaken in this thesis confirms an absence of electrophysiological changes with stretch except under extreme conditions suggesting that MEF is not a robust and necessarily repeatable phenomenon in the mammalian heart. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320476 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

The cytoskeleton is a diverse, multi-protein framework that plays a fundamental role in many cellular activities including mitosis, cell division, intracellular transport, cell motility, muscle contraction, and the regulation of cell polarity and organization. Furthermore, cytoskeletal filaments have been implicated in the pathogenesis of a wide variety of diseases including cancer, blood disease, cardiovascular disease, inflammatory disease, neurodegenerative disease, and problems with skin, nail, cornea, hair, liver and colon. Increasing evidence suggests that the distribution and organization of the cytoskeleton in living cells are affected by mechanical stresses and the cytoskeleton determines cell stiffness. We developed a fully nonlinear, constrained mixture model for adherent cells that allows one to account separately for the contributions of the primary structural constituents of the cytoskeleton and extended a prior solution from the finite elasticity literature for use in a sub-class of atomic force microscopy (AFM) studies of cell mechanics. The model showed that the degree of substrate stretch and the geometry of the AFM tip dramatically affect the measured cell stiffness. Consistent with previous studies, the model showed that disruption of the actin filaments can reduce the stiffness substantially, whereas there can be little contribution to the overall cell stiffness by the microtubules or intermediate filaments. To investigate the effect of mechanical stretching on cytoskeletal remodeling and cell stiffness, we developed a simple cell-stretching device that can be combined with an AFM and confocal microscopy. Results demonstrate that cyclic stretching significantly and rapidly alters both cell stiffness and focal adhesion associated vinculin and paxillin, suggesting that focal adhesion remodeling plays a critical role in cell stiffness by recruiting and anchoring F-actin. Finally, we estimated cytoskeletal remodeling by synthesizing data on stretch-induced dynamic changes in cell stiffness and focal adhesion area using constrained mixture approach. Results suggest that the acute increase in stiffness in response to an increased cyclic stretch was probably due to an increased stretch of the original filaments whereas the subsequent decrease back towards normalcy was consistent with a replacement of the highly stretched original filaments with less stretched new filaments.

The interactions between laminar premixed flames and counter-rotating vortex pairs in natural and synthetic gas mixtures have been computationally investigated through the use of Direct Numerical Simulations and parallel processing. Using a computational model for premixed combustion, laminar flames are simulated for single- and two-component fuel mixtures of methane, carbon monoxide, and hydrogen. These laminar flames are forced to interact with superimposed laminar vortex pairs, which mimic the effects of a pulsed, two-dimensional slot-injection. The premixed flames are parameterized by their unstretched laminar flame speed, heat release, and flame thickness. The simulated vortices are of a fixed size (relative to the flame thickness) and are parameterized, solely, by their rotational velocity (relative to the flame speed). Strain rate and surface curvature measurements are made along the stretched flame surfaces to study the effects of additive syngas species (CO and H2) on lean methane-air flames. For flames that share the same unstretched laminar flame speed, heat release, and flame thickness, it is observed that the effects of carbon monoxide on methane-air mixtures are essentially negigible while the effects of hydrogen are quite substantial. The dynamics of stretched CH4/Air and CH4/CO/Air flames are nearly identical to one another for interactions with both strong and weak vortices. However, the CH4/H2/Air flames demonstrate a remarkable tendency toward surface area growth. Over comparable interaction periods, the flame surface area produced during interactions with CH4/H2/Air flames was found to be more than double that of the pure CH4/Air flames. Despite several obvious differences, all of the interactions revealed the same basic phenomena, including vortex breakdown and flame pinch-off (i.e. pocket formation). In general, the strain rate and surface curvature magnitudes were found to be lower for the CH4/H2/Air flames, and comparable between CH4/Air and CH4/CO/Air flames. Rates of flame stretching are not explicitely determined, but are, instead, addressed through observation of their individual components. Two different models are used to determine local displacement speed values. A discrepancy between practical and theoretical definitions of the displacement speed is evident based on the instantaneous results for CH4/Air and CH4/H2/Air flames interacting with weak and strong vortices.

Skeletal muscle has an integral role in many activities. Although mechanical stretch and active force generation are known to be required for the maintenance of healthy muscle function, the mechanism by which those signals mediate muscle growth is unknown. This project was based on the hypothesis that stretch and force generation activate the Calcineurin/NFAT pathway and induce Cox-2 expression and initiate muscle hypertrophy. The specific aims of this study were to 1) develop a minimally invasive system capable of initiating hypertrophic signaling in mice, 2) characterize the effects of isometric activation, passive lengthening, and active lengthening on signaling cascades, and 3) determine the involvement of the Calcineurin/NFAT pathway and activation of COX-2 gene expression. We propose a pathway in which stimuli increase intracellular calcium, which activates the phosphatase calcineurin. Calcineurin dephosphorylates NFAT, which is translocated into the nucleus and initiates transcription of the COX-2 gene. COX-2 mediated synthesis of PGG2 is the rate-limiting step in bioactive prostaglandin synthesis. Prostaglandins then stimulate known hypertrophic signals including the PI-3 Kinase and MAP Kinase signaling cascades.

Abstract This study aims to measure the flow field distribution in a microchannel with different heights adjusted. Two different materials, PDMS and Coverglass, were used to observe the flow velocity distribution change resulting from the difference in Zeta potential. The velocity distribution data were also obtained. In the experiment, 1¡Ñ TBE buffer solution with viscosity of 1 cp was used with the electric field intensity controlled under 5, 7.5 and 10 kV/m, respectively. Micrometer resolution Particle Image Velocimetry (£gPIV) was used to measure partial velocity distribution in order to explore the hydrodynamic stretch effect on DNA molecules when the microchannel, where the solution was placed, was adjusted to different heights. This study also statistically analyzed the stretch length distribution of DNA molecules in the microchannel and calculated the time of DNA molecule deformation and stress relaxation time in order to understand the stretch condition under different heights as well as the stretch and deformation of DNA molecules in microchannels.

The cytoskeleton is a diverse, multi-protein framework that plays a fundamental role in many cellular activities including mitosis, cell division, intracellular transport, cell motility, muscle contraction, and the regulation of cell polarity and organization. Furthermore, cytoskeletal filaments have been implicated in the pathogenesis of a wide variety of diseases including cancer, blood disease, cardiovascular disease, inflammatory disease, neurodegenerative disease, and problems with skin, nail, cornea, hair, liver and colon. Increasing evidence suggests that the distribution and organization of the cytoskeleton in living cells are affected by mechanical stresses and the cytoskeleton determines cell stiffness. We developed a fully nonlinear, constrained mixture model for adherent cells that allows one to account separately for the contributions of the primary structural constituents of the cytoskeleton and extended a prior solution from the finite elasticity literature for use in a sub-class of atomic force microscopy (AFM) studies of cell mechanics. The model showed that the degree of substrate stretch and the geometry of the AFM tip dramatically affect the measured cell stiffness. Consistent with previous studies, the model showed that disruption of the actin filaments can reduce the stiffness substantially, whereas there can be little contribution to the overall cell stiffness by the microtubules or intermediate filaments. To investigate the effect of mechanical stretching on cytoskeletal remodeling and cell stiffness, we developed a simple cell-stretching device that can be combined with an AFM and confocal microscopy. Results demonstrate that cyclic stretching significantly and rapidly alters both cell stiffness and focal adhesion associated vinculin and paxillin, suggesting that focal adhesion remodeling plays a critical role in cell stiffness by recruiting and anchoring F-actin. Finally, we estimated cytoskeletal remodeling by synthesizing data on stretch-induced dynamic changes in cell stiffness and focal adhesion area using constrained mixture approach. Results suggest that the acute increase in stiffness in response to an increased cyclic stretch was probably due to an increased stretch of the original filaments whereas the subsequent decrease back towards normalcy was consistent with a replacement of the highly stretched original filaments with less stretched new filaments.

The most basic property of a muscle is its ability to contract and produce force when stimulated. A muscle is mainly composed of cells consisting of myofibrils with its basic unit called as a sarcomere. A sarcomere is composed of actin and myosin responsible for the muscle contraction. The Hill-type muscle model is the most commonly used model to simulate the behavior of a muscle. A muscle can produce its maximum force at isometric conditions. The level of force produced in the muscle is determined by the the frequency of the signals from the CNS. The force production is also a function of force-muscle current velocity and force-muscle current length relations. A muscle contains two types of sensors / i.e. muscle spindle and golgi tendon organ, which give rise to the feedback control of the muscle length and muscle contraction velocity. In this study a 1-D model of a muscle is formed step by step in Simulink. In the models the muscle mechanics has been investigated and the results are compared with the previous works.

Aortic valve disease is among the third most common cardiovascular disease worldwide, and is also a strong predictor for other cardiac related deaths. Altered mechanical forces are believed to cause changes in aortic valve biosynthetic activity, eventually leading to valve disease, however little is known about the cellular and molecular events involved in these processes. To gain a fundamental understanding into aortic valve disease mechanobiology, an ex vivo experimental model was used to study the effects of normal and elevated cyclic stretch on aortic valve remodeling and degenerative disease. The hypothesis of this proposal was that elevated cyclic stretch will result in increased expression of markers related to degenerative valve disease. Three aspects of aortic valve disease were studied: (i) Altered extracellular matrix remodeling; (ii) Aortic Valve Calcification; and (iii) Serotonin-induced valvulopathy. Results showed that elevated stretch resulted in increased matrix remodeling and calcification via a bone morphogenic protein-dependent pathway. In addition, elevated stretch and serotonin resulted in increased collagen biosynthesis and tissue stiffness via a serotonin-2A receptor-mediated pathway. This work adds to current knowledge on aortic valve disease mechanisms, and could pave the way for the development of novel treatments for valve disease and for the design of tissue engineered valve constructs.